Hyaluronic acid in soft gel form

ABSTRACT

An orally administered soft gelatin formulation preparation of low molecular weight Hyaluronic Acid (HA) for use as a nutritional supplement to provide the primary benefit of internally causing the softening of the human skin.

CROSS REFERENCE TO RELATED APPLICATION

[0001] This application is a continuation of and claims priority to U.S.application Ser. No. 10/035,753, filed Dec. 21, 2001, the contents ofwhich are incorporated herein by reference.

FIELD OF THE INVENTION

[0002] The present invention concerns an orally administered preparationof a composition of Hyaluronic Acid (HA) for use as a nutritionalsupplement with benefits of softening the human skin.

BACKGROUND OF THE INVENTION

[0003] Hyaluronic Acid is a naturally occurring high molecular weightpolysaccharide having an empirical formula of C₁₄H₂₀NNa₁₁ where n>1000.It is accepted that Hyaluronic Acid (HA) comes from three principlesources, human umbilical cords, rooster combs, and certain bacterialcultures from group A and C hemolytic streptococci. Commercial sourcesfor HA are generally from umbilical cords and rooster combs. The presentinvention is derived from rooster combs.

[0004] HA was first isolated by Karl Meyer in 1934. He derived the novelglycosoaminoglycan from the vitreous of bovine eyes. The substancecontained a uronic acid and an amino sugar, but no sulfoesters. Meyer'sdiscovery is frequently referred to as Hylauron in vivo and HyaluronicAcid (HA) ex vivo. The precise chemical structure was determined 20years later and classified as part of biologically active moleculesknown as glycosoaminoglycans (GAGs). GAGs are principally located in oron the cellular membrane or in the material between cells called theextracellular matrix (ECM).

[0005] GAGs are long, unbranched polysaccharides containing a repeatingdisaccharide unit. In the case of Hyaluronan this disaccharide consistsof D-glucuronate and D-acetylglucosamine. GAGs are negatively charged,high molecular weight molecules that have several unique properties.

[0006] Among them is high viscosity in solution. High viscosity yieldslow compressibility resulting in excellent lubrication and shockabsorption, particularly for soft tissues and joints. HA polymers arecomparatively very large (i.e., having high molecular weight in therange of 1 million to 4 million daltons in a highly polymerizedpreparation) and can displace a large volume of water making them thebody's premier lubricators.

[0007] HA is found in many tissues of the body. It is present inparticularly high concentrations in the synovial fluid that lubricatesthe joints, in heart valve tissue, in the fluids of the inner ear, inmany layers of the skin, especially the dermis, and in the vitreoushumor of the eyes.

[0008] The preparation HA from rooster combs and human umbilical cordsfor use in eye and joint applications is described in U.S. Pat. No.4,141,973 to E. A. Balazs. This patent provides a detailed review of thetechnical literature describing the isolation, characterization and usesof HA. U.S. Pat. No. 4,303,676 also to E. A. Balazs describes thecosmetic formulations containing Hyaluronate fractions in variousmolecular weight ranges made from rooster combs. U.S. Pat. No. 4,328,803to L. G. Pape describes the use of an ultra-pure Hyaluronic Acid saltutilized in eye surgery. The HA product used here was a sodiumHyaluronate salt available under the registered trademark HYARTIL.RTMfrom Pharmacia, Inc. and obtained in commercial quantities from roostercombs as well.

[0009] The purpose it has in each of these applications is slightlydifferent, but all are based on the principles of cellular hydration andseparation. The hydration provided by HA allows for the proper transferof nutrition and elimination of waste. In a sense, cells are bathed in aframework of HA. This framework allows the exchange of not justnutrition, but also regulatory and communication chemicals through thespace between cells. Until recently, it was thought that HA was largelyinert, that it simply filled the space between cells. This space, calledthe extra cellular matrix (ECM) is filled with a ground substance. Theground substance is primarily HA.

[0010] As Meyer observed when discussing sulfoesters, HA is unique amongthe GAGs because it does not contain sulfate and is not bonded toproteins as a proteoglycan. It is, however, a component of proteoglycansin the ECM. This gives HA great flexibility in providing scalablestructural integrity through visco-elastic support necessary forseparation between tissues while facilitating immune functions orintercellular communication. HA in the ECM helps control tissuepermeation, bacterial invasiveness, and macromolecular transport betweencells. HA also plays an important role in mediating how cells ofneighboring tissues interact and communicate.

[0011] The body's need for HA is great. Not only is it an important partof tissue structure, but it also provides active support and bindingsites for intracellular interactions, acts as a buffer zone to protectcells, and forms part of the waste complexes that is frequentlyeliminated from tissues frequently. Because of this, HA is catabolizedin many tissues and must be renewed constantly.

[0012] Certain cells such as chondrocytes in the cartilage andkeratinocytes in the epidermis actively synthesize and catabolize HAthroughout a person's life span. Hascall et al. has found that thehalf-life of an HA molecule to be normally 2-3 weeks, while thehalf-life in the epidermis is amazingly less than one day. Thisproduction decreases with a person's increased age. Any means ofincreasing the amount of HA in the body promises to have great benefitsin improving the quality, elasticity, and function of the skin andjoints. Till now, large/high molecular weight HA has been topicallyapplied in cosmetic products and injected in medical preparations forjoint health.

[0013] Other attempts take the form of supplementing with HA components,namely chondroitin and glucosamine. While these are both effective inhelping to augment the functions of HA in the joints, they have not beenproven to assist in the intercellular functions of HA nor do they affectHA levels directly as far as it is known.

SUMMARY OF THE INVENTION

[0014] One of the difficulties in trying to increase the amount ofavailable HA in the body is the size of the molecule. The largepolymeric structure that grants HA its uniqueness, makes it difficult toacquire from outside the body. These large structures simply cannot passfrom the digestive system to the blood stream. As a result mostexogenous supplementation use of HA has been in the form of injection ortopical application.

[0015] The present invention concerns an orally administered softgelatin formulation that contains 35 to 45 mg of HA derived from 400 to430 mg of an extract containing a concentration of 9% HA. The nameINJUV™ has been selected as the trademark for the soft gelatine form ofthe present invention. The soft gel form makes it stable in retainingthe properties of HA and the small molecular weight produces abioavailable product able to be absorbed through digestion.

[0016] Other features and advantages of the present invention willbecome more apparent from the following detailed description, whichillustrate, by way of example, the principles of the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0017] The present invention is a soft gelatin, ingestible formulationof Hyaluronic Acid with low molecular weight. The composition is an oralpreparation of between 35 to 45 mg dosage of low molecular weight(preferably between 50,000 to 200,000 daltons) Hyaluronic Acid (HA)derived from 400 to 430 mg of an extract containing approximately 9%concentration of HA. Injuv™ is selected as the commercial name andtrademark for the preferred embodiment or formulation of the presentinvention that can be placed in a soft gelatin capsule having a dosageof approximately 38 mg of low molecular weight HA that is derived fromapproximately 420 mg of an extract containing approximately 9%concentration of HA. The present invention provides an oral dose form ofHA which uses an enzyme cleaving technique and takes naturally derivedHyaluronic Acid and breaks it down to lower molecular weight polymerscapable of absorption thorough oral administration via a soft gelatincapsule. The product can be taken every day as a dietary supplement foran indefinite period of time with benefits of softening of the humanskin.

[0018] The manufacturing process of the present invention is as follows:

[0019] Melt Beeswax in rice Bran Oil;

[0020] Heat to a minimum of 60 degrees Celsius;

[0021] Allow to cool to 30 degrees celsius and add Hyaluronic Acid;

[0022] Mix for a minimum of thirty minutes;

[0023] Ensure that the mixture is homogenous and that no air remains;and

[0024] Encapsulate mixture in soft gelatin capsule.

[0025] A variety of further modifications and improvements in and to thepresent invention will be apparent to persons skilled in the art.Accordingly, no limitation on the invention is intended by way of theforegoing description, except as set forth in the appended claims.

What is claimed:
 1. An orally administered composition comprisinghyaluronic acid having a dosage of between 35 to 45 and a low molecularweight of between 50,000 to 200,000 daltons.
 2. A soft gel capsulecontaining hyaluronic acid, prepared by a process comprising the stepsof: a) melting beeswax in rice bran oil; b) adding hyaluronic acid tothe melted beeswax in rice bran oil, thereby forming a mixture; c)stirring the mixture; and d) encapsulating the mixture in a soft gelcapsule.
 3. The soft gel capsule of claim 2, wherein the dosage ofhyaluronic acid is between about 35 to about 45 mg of hyaluronic acid.4. The soft gel capsule of claim 2, wherein the hyaluronic acid has amolecular weight of between 50,000 and 200,000 daltons.
 5. The soft gelcapsule of claim 2, wherein the dosage of hyaluronic acid is derivedfrom an extract containing about 9% hyaluronic acid.
 6. The soft gelcapsule of claim 2, wherein the hyaluronic acid is derived from thecombs of roosters.
 7. The soft gel capsule of claim 2, wherein thedosage of hyaluronic acid is between about 35 to about 45 mg ofhyaluronic acid and the hyaluronic acid has a molecular weight ofbetween 50,000 and 200,000 daltons.
 8. A soft gel capsule containinghyaluronic acid, prepared by a process comprising the steps of: a)adding hyaluronic acid to rice bran oil, thereby forming a mixture; b)stirring the mixture; and c) encapsulating the mixture in a soft gelcapsule.
 9. The soft gel capsule of claim 8, wherein the dosage ofhyaluronic acid is between about 35 to about 45 mg of hyaluronic acid.10. The soft gel capsule of claim 8, wherein the hyaluronic acid has amolecular weight of between 50,000 and 200,000 daltons.
 11. The soft gelcapsule of claim 8, wherein the dosage of hyaluronic acid is derivedfrom an extract containing about 9% hyaluronic acid.
 12. The soft gelcapsule of claim 8, wherein the hyaluronic acid is derived from thecombs of roosters.
 13. The soft gel capsule of claim 8, wherein thedosage of hyaluronic acid is between about 35 to about 45 mg ofhyaluronic acid and the hyaluronic acid has a molecular weight ofbetween 50,000 and 200,000 daltons.
 14. A soft gel capsule containinghyaluronic acid, prepared by a process comprising the steps of: a)melting beeswax; b) adding hyaluronic acid to the melted beeswax,thereby forming a mixture; c) stirring the mixture; and d) encapsulatingthe mixture in a soft gel capsule.
 15. The soft gel capsule of claim 14,wherein the dosage of hyaluronic acid is between about 35 to about 45 mgof hyaluronic acid.
 16. The soft gel capsule of claim 14, wherein thehyaluronic acid has a molecular weight of between 50,000 and 200,000daltons.
 17. The soft gel capsule of claim 14, wherein the dosage ofhyaluronic acid is derived from an extract containing about 9%hyaluronic acid.
 18. The soft gel capsule of claim 14, wherein thehyaluronic acid is derived from the combs of roosters.
 19. The soft gelcapsule of claim 14, wherein the dosage of hyaluronic acid is betweenabout 35 to about 45 mg of hyaluronic acid and the hyaluronic acid has amolecular weight of between 50,000 and 200,000 daltons.